Solid phase organic synthesis (SPOS) offers considerable advantages compared to traditional solution phase reactions. In particular, solid phase reactions are very attractive for combinatorial and parallel work because of the relative ease of purification of the resin bound material after each reaction step. Purification can be performed by simple washing and filtration. (see e.g., Obrecht and Villalgordo: Solid-Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries, Pergamon, 1998).
Since virtually every endogenous and synthetic ligand that interacts with receptors in the central nervous system contains a basic functionality, most often a tertiary or secondary amino group, SPOS methods for the preparation of such compounds remains an extremely important aspect of medicinal chemistry aimed at central nervous system active drugs.
The solid phase organic synthesis of tertiary amines, using the nitrogen as the point of attachment to the solid support, is known in the art. (See FIG. 1) However, the methods described in previous work have disadvantages related to the lability of the linkers used as well as the release reactions.